Singh Vikash, Davidson Anthony C, Hume Peter J, Humphreys Daniel, Koronakis Vassilis
Department of Pathology, University of Cambridge , Cambridge , UK.
Department of Biomedical Science, University of Sheffield , Sheffield , UK.
Small GTPases. 2019 Nov;10(6):411-418. doi: 10.1080/21541248.2017.1329691. Epub 2017 Nov 3.
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis. This provides insight into Arf regulation of the actin cytoskeleton, while putting the spotlight on small GTPase cooperation with emerging evidence of its importance in fundamental cell biology and interactions with pathogenic bacteria.
小GTP酶的Arf和Rho亚家族是核苷酸依赖性分子开关，作为囊泡运输和肌动蛋白细胞骨架组织的主要调节因子。小GTP酶通过与称为效应器的不同结合伙伴库相互作用，以高保真度控制细胞过程。虽然我们对这些GTP酶如何单独发挥作用了解很多，但对于它们如何协同作用，尤其是在效应器的控制方面，了解相对较少。这篇综述强调了Arf GTP酶如何与Rac1合作，通过招募和激活波调节复合物（WRC）来调节膜上的肌动蛋白细胞骨架动力学，WRC是一种Rho效应器，是片状伪足形成和巨胞饮作用的基础。这为Arf对肌动蛋白细胞骨架的调节提供了见解，同时随着小GTP酶合作在基础细胞生物学中的重要性以及与病原菌相互作用的新证据的出现，将焦点放在了小GTP酶的合作上。
